Ask about this productRelated genes to: RRAGC antibody
- Gene:
- RRAGC NIH gene
- Name:
- Ras related GTP binding C
- Previous symbol:
- -
- Synonyms:
- GTR2, FLJ13311
- Chromosome:
- 1p34.3
- Locus Type:
- gene with protein product
- Date approved:
- 2003-07-07
- Date modifiied:
- 2016-10-05
Related products to: RRAGC antibody
Related articles to: RRAGC antibody
- Pharmacodynamic biomarkers of sirolimus were investigated using omics analysis of tear fluids from Japanese patients with meibomian gland dysfunction (MGD). - Source: PubMed
Publication date: 2026/03/27
Zhou LeiShimizu HiroyukiTogashi YukiKirihara TomokoYang YuhanLam Chuen ThomasShimada HisaoTong Louis - TFEB (transcription factor EB) is a critical regulator of lysosomal biogenesis, macroautophagy/autophagy and energy homeostasis through controlling expression of genes belonging to the coordinated lysosomal expression and regulation network. AMP-activated protein kinase (AMPK) has been reported to phosphorylate TFEB at three conserved C-terminal serine residues (S466, S467, S469) and these phosphorylation events were reported to be essential for transcriptional activation of TFEB. In sharp contrast to this proposition, we demonstrate that AMPK activation leads to the dephosphorylation of the C-terminal sites. We show that a synthetic peptide encompassing the C-terminal serine residues of TFEB is a poor substrate of AMPK in vitro. Treatment of cells with an AMPK activator (MK-8722), glucose deprivation or MTOR inhibitor (torin1) robustly dephosphorylated TFEB not only at the MTORC1-targeted N-terminal serine sites, but also at the C-terminal sites. Loss of function of AMPK abrogated MK-8722- but not torin1-induced dephosphorylation and induction of the TFEB target genes. AMPK: 5'-adenosine monophosphate-activated protein kinase; ACAC/ACC: acetyl-CoA carboxylase; AICAR: 5-aminoimidazole-4-carbox-amide ribonucleotide; CLEAR: coordinated lysosomal expression and regulation; DKO: double knockout; DMEM: Dulbecco's modified Eagle's medium; DMSO: dimethyl sulfoxide; DQ-BSA: self-quenched BODIPY® dye conjugates of bovine serum albumin; KI: knock-in; KO: knockout; MEFs: mouse embryonic fibroblasts; MTORC1: mechanistic target of rapamycin kinase complex 1; RRAGC: Ras related GTP binding C; RPTOR: regulatory associated protein of MTOR complex 1; RPS6KA/RSK: ribosomal protein S6 kinase A; RPS6KB1/S6K1: ribosomal protein S6 kinase B1; RT-qPCR: reverse transcription quantitative polymerase chain reaction; TFE3: transcription factor binding to IGHM enhancer 3; TFEB: transcription factor EB; ULK1: unc-51 like autophagy activating kinase 1; WT: wild-type. - Source: PubMed
Publication date: 2026/02/23
Negoita FlorentinaFraguas Bringas ConchitaHellberg KristinaLuda Katarzyna MLiu HonglingLi ZhiyuanCuenco JoycelineZhao Jin-FengSathe GajananGanley Ian GSapkota Gopal PSakamoto Kei - Bilirubin-induced brain damage represents a serious clinical consequence of hyperbilirubinemia, yet the role and underlying molecular mechanisms of autophagy the remain largely elusive. Here, we demonstrate that, for the first time, N6-methyladenosine (m6A) demethylase AlkB homolog 5 (ALKBH5) mediated dysregulated autophagic flux contributes to bilirubin-induced neurotoxicity. Hyperdifferential differentiated PC12 cells and neonatal Sprague-Dawley rats were employed as in vitro and in vivo models, respectively. In vivo experiments first showed a dysregulated autophagy and neuronal damage in hyperbilirubinemia. In vitro further experiments observed that bilirubin exposure inhibited autophagy as illustrated by the downregulated p62 and LC3-II protein expression and transmission electron microscopy results. Furthermore, we found that the autophagic flux impairment was due to the inhibition of initial stage following bilirubin exposure, which was pharmacologically validated using rapamycin and bafilomycin A1 and up-regulated protein expression of p-mTOR and BCL2. More importantly, we found that ALKBH5 overexpression can exacerbate bilirubin-induced autophagic flux damage, whereas ALKBH5 knockdown attenuated the inhibited autophagic flux damage. Mechanistically, Vacuole membrane protein 1 (VMP1), Ras-related GTP-binding protein C (RRAGC), and protein kinase AMP-activated catalytic subunit alpha 1 (PRKAA1) were identified as the target genes of ALKBH5 to impair autophagic flux with mRNA stability assay, RT-PCR analysis, and bioinfomatic analysis, thereby promoting bilirubin-induced neurotoxicity. Collectively, our findings reveal that ALKBH5 participates in bilirubin-induced autophagic flux impairment, and propose m6A-dependent autophagy as a potential therapeutic target in hyperbilirubinemia. - Source: PubMed
Publication date: 2026/01/28
Zhou JinfuLiao SiningZhang ChenranLi GuilinZheng FuliYu GuangxiaHu HongShao WenyaGuo ZhenkunWu SiyingTang JianpingLi Huangyuan - Proteotoxic stress, arising from conditions that cause misfolded protein accumulation, is closely linked to the pathogenesis of multiple diseases. Macroautophagy/autophagy activation is considered a compensatory mechanism to maintain protein homeostasis, but the underlying regulatory mechanisms remain incompletely understood. Here, we show that proteotoxic stress induced by proteasome inhibition, puromycin treatment, or polyglutamine-expanded HTT (huntingtin) expression promotes nuclear accumulation of TFEB and TFE3, key regulators of lysosomal biogenesis and autophagy. Mechanistically, TFEB activation under proteotoxic stress occurs independently of canonical MTORC1 inactivation mediated by TSC2 or ATF4. Instead, it involves non-canonical inhibition of MTORC1 via RRAG GTPases. Proteotoxic stress disrupts the RRAGC-TFEB interaction, preventing TFEB recruitment to lysosomes and subsequent MTORC1 phosphorylation. An activated RRAGC mutant rescues impaired lysosomal localization and nuclear accumulation of TFEB, while co-overexpression of FLCN and FNIP2, a GAP for RRAGC, partially restores stress-induced TFEB dephosphorylation. In addition, proteasome inhibition activates non-canonical autophagy. Deletion of or , which known blocks Atg8-family protein lipidation and sequesters the FLCN-FNIP2 complex, partially abolishes proteotoxic stress-induced TFEB dephosphorylation and nuclear accumulation. Together, these findings demonstrate that proteotoxic stress triggers both non-canonical autophagy and TFEB-mediated canonical autophagy, with Atg8-family protein lipidation contributing to TFEB activation. Our results provide novel insights into how proteotoxic stress engages non-canonical MTORC1 inhibition and TFEB activation, thereby enhancing understanding of cellular adaptation to proteotoxic stress.: ALP, autophagy-lysosomal pathway; ATF4, activating transcription factor 4; Baf A1, bafilomycin A; CHX, cycloheximide; BTZ, bortezomib; CFZ, carfilzomib; CQ, chloroquine; CTSB, cathepsin B; CTSD, cathepsin D; DQ-BSA, dequenched-bovine serum albumin; EIF4EBP1/4EBP1, eukaryotic translation initiation factor 4E binding protein 1; ER, endoplasmic reticulum; MAP1LC3B/LC3B, microtubule associated protein 1 light chain 3 beta; MG132, carbobenzoxy-Leu-Leu-leucinal; MTORC1, mechanistic target of rapamycin kinase complex 1; RPS6KB1/p70, ribosomal protein S6 kinase B1; RRAG, Ras related GTP binding; SQSTM1/p62, sequestosome 1; TFE3, transcription factor E3; TFEB, transcription factor EB; TSC2, TSC complex subunit 2; tfLC3, tandem fluorescent LC3; UPS, ubiquitin-proteasome system. - Source: PubMed
Publication date: 2026/01/14
Zhu ZhouYang JingMontefusco SandroXia SiyuOu JinhuanTong HaiboZeng QingzhongXu FengmeiDai LingyunSun JichaoXu ChengchaoMedina Diego LuisWang JigangZhang WeiYang Chuanbin - Autoimmune hepatitis (AIH), a severe immune-mediated liver disease resulting from defective immune tolerance, was thought to be caused by monogenic predisposition with possible external triggers. The development of AIH in monogenic primary immune deficiencies prompted us to search for causative genetic defects in AIH. - Source: PubMed
Publication date: 2025/09/16
Gaigne Léa-PhilippineBesnard CarolineDebeaupuis OrianneDegtiar ArtemNhat Duong HoStolzenberg Marie-ClaudeCamara FatouPellé OlivierSchvartz AdrienPerin MélodieAlmes MarionDarmellah-Remil AmariaGonzales EmmanuelGardin AntoineHabes DalilaDestombe SylvieDe Martin EleonoraDuclos-Vallée Jean-CharlesArkwright Peter DRieux-Laucat FrédéricJacquemin EmmanuelMagerus Aude